CXC chemokine receptor 4 (CXCR4) blockade in cancer treatment

Bao, Suhong; Darvishi, Mohammad; Amin, Ali H.; Al-Haideri, Maysoon; Patra, Indrajit; Kashikova, Khadisha; Ahmad, Irfan; Alsaikhan, Fahad; Al‐qaim, Zahraa Haleem; Al‐Gazally, Moaed E.; Kiasari, Bahman Abedi; Tavakoli‐Far, Bahareh; Sidikov, Akmal A; Mustafa, Yasser Fakri; Akhavan‐Sigari, Reza

doi:10.1007/s00432-022-04444-w

Cited by 7 publications

(5 citation statements)

References 279 publications

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“…Activation of this receptor by the cognate ligand, CXCL12, promotes tumor cell proliferation, survival, and metastasis. Inhibition of CXCR4 results in enhanced T and NK cell infiltration with reduced recruitment of TAFs 75 . Another study reported that CD56 + NK cells were absent in the TME of PMP, which also supports the immunosuppressive nature of the microenvironment 59 .…”

Section: Immunologic Features Of the Pmp Tmementioning

confidence: 99%

Progress on immuno-microenvironment and immune-related therapies in patients with pseudomyxoma peritonei

Zhao,

Wei,

et al. 2024

Cancer Biol Med

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Pseudomyxoma peritonei (PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy (CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit (GNAS). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radio-immunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.

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Section: Immunologic Features Of the Pmp Tmementioning

confidence: 99%

Progress on immuno-microenvironment and immune-related therapies in patients with pseudomyxoma peritonei

Zhao,

Wei,

et al. 2024

Cancer Biol Med

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“…Therefore, CXCR4 has become an important target for tumor therapy. CXCR4 is widely expressed in various types of cells in the tumor microenvironment, such as tumor cells, T cells, B cells, dendritic cells, myeloid-derived suppressor cells, and vascular endothelial cells that are activated in response to the release of chemokine CXCL12 from tumor cells and stromal cells in the tumor microenvironment, which provides a molecular biological basis for the integrated diagnosis and treatment of tumors with high CXCR4 expression. , …”

Section: Introductionmentioning

confidence: 99%

“…6 Overactivation of CXCR4 has been demonstrated in more than 20 different tumor types and is closely associated with tumor progression and metastasis, poor prognosis, and chemotherapy resistance by promoting angiogenesis, cell metastasis, growth, and survival. 7,8 To date, CXCL12 (C-X-C chemokine ligand 12, also known as SDF-1) is the only endogenous CXCR4 ligand and a member of the CXC chemokine family. 9 The CXCL12/CXCR4 signaling axis can regulate the proliferation of tumor cells by activating signaling pathways in tumor cells.…”

Section: Introductionmentioning

confidence: 99%

“…CXCR4 is widely expressed in various types of cells in the tumor microenvironment, such as tumor cells, T cells, B cells, dendritic cells, myeloid-derived suppressor cells, and vascular endothelial cells that are activated in response to the release of chemokine CXCL12 from tumor cells and stromal cells in the tumor microenvironment, which provides a molecular biological basis for the integrated diagnosis and treatment of tumors with high CXCR4 expression. 7,8 CPCR4 is a pentacyclic peptide with the sequence cyclo (-D-Tyr-n-me-D-Orn-L-Arg-L-2-NAL-Gly-). 13 Pentixafor (DOTA-CPCR4) is the first PET precursor to target CXCR4 and has succeeded greatly.…”

Section: Introductionmentioning

confidence: 99%

“…Chemokine (C-X-C motif) receptor 4 (CXCR4) is a G-protein-coupled receptor (GPCR) with seven transmembrane structures composed of 352 amino acids involved in regulating important physiological mechanisms in the body. , CXCR4 has been reported to be involved in the entry of human immunodeficiency virus into CD4 + T cells and subsequently is involved in developing various diseases, such as cancer, autoimmune defects, atherosclerosis, and neurodegenerative diseases . Overactivation of CXCR4 has been demonstrated in more than 20 different tumor types and is closely associated with tumor progression and metastasis, poor prognosis, and chemotherapy resistance by promoting angiogenesis, cell metastasis, growth, and survival. , To date, CXCL12 (C-X-C chemokine ligand 12, also known as SDF-1) is the only endogenous CXCR4 ligand and a member of the CXC chemokine family . The CXCL12/CXCR4 signaling axis can regulate the proliferation of tumor cells by activating signaling pathways in tumor cells .…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Screening, and Evaluation of Theranostic Molecular CPCR4-Based Probe Targeting CXCR4

Yang,

Shi,

Lin

et al. 2024

Mol. Pharmaceutics

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Chemokines and chemokine receptors are indispensable to play a key role in the development of malignant tumors. As one of the most widely expressed chemokine receptors, chemokine (C-X-C motif) receptor 4 (CXCR4) has been a popular research focus. In most tumors, CXCR4 expression is significantly upregulated. Moreover, integrated nuclide diagnosis and therapy targeting CXCR4 show great potential. [ 68 Ga]Ga-pentixafor, a radioligand targeting CXCR4, exhibits a strong affinity for CXCR4 both in vivo and in vitro. However, [ 177 Lu]Lu-pentixather, the therapeutic companion of [ 68 Ga]Ga-pentixafor, requires significant refinement to mitigate its pronounced hepatic biodistribution. The objective of this study was to synthesize theranostic molecular tracers with superior CXCR4 targeting functions. The Daudi cell line, which highly expressed CXCR4, and the MM.1S cell line, which weakly expressed CXCR4, were used in this study. Based on the pharmacophore cyclo (-D-Tyr-n-me-D-Orn-L-Arg-L-2-NAL-Gly-) (CPCR4) of pentixafor, six tracers were synthesized: [ 124 I]I-1 ([ 124 I]I-CPCR4), [ 99m Tc]Tc-2 ([ 99m Tc]Tc-HYNIC-CPCR4), [ 124 I]I-3 ([ 124 I]I-pentixafor), [ 18 F]AlF-4 ([ 18 F]AlF-NETA-CPCR4), [ 99m Tc]Tc-5 ([ 99m Tc]Tc-MAG 3 -CPCR4) and [ 124 I]I-6 ([ 124I]Ipentixafor-Ga) and their radiochemical purities were all higher than 95%. After positron emission tomography (PET)/single-photon emission computed tomography (SPECT) imaging, the [ 124 I]I-6 group exhibited the best target-nontarget ratio. At the same time, comparing the [ 68 Ga]Ga-pentixafor group with the [ 124 I]I-6 group, we found that the [ 124 I]I-6 group had a better target-nontarget ratio and lower uptake in nontarget organs. Therefore, compound 6 was selected for therapeutic radionuclide ( 131 I) labeling, and the tumor-bearing animal models were treated with [ 131 I]I-6. The volume of the tumor site was significantly reduced in the treatment group compared with the control group, and no significant side effects were found. [ 124 I]I-6 and [ 131 I]I-6 showed excellent affinity for targeting CXCR4, and they showed great potential for the integrated diagnosis and treatment of tumors with high CXCR4 expression.

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CD38/NAD+ glycohydrolase and associated antigens in chronic lymphocytic leukaemia: From interconnected signalling pathways to therapeutic strategies

Bauvois,

Nguyen-Khac,

Merle-Béral

et al. 2024

Biochimie

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CXC chemokine receptor 4 (CXCR4) blockade in cancer treatment

Cited by 7 publications

References 279 publications

Progress on immuno-microenvironment and immune-related therapies in patients with pseudomyxoma peritonei

Progress on immuno-microenvironment and immune-related therapies in patients with pseudomyxoma peritonei

Synthesis, Screening, and Evaluation of Theranostic Molecular CPCR4-Based Probe Targeting CXCR4

CD38/NAD+ glycohydrolase and associated antigens in chronic lymphocytic leukaemia: From interconnected signalling pathways to therapeutic strategies

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